COX-2-deficient mice are less prone to MPTP-neurotoxicity... : NeuroReport (original) (raw)

MOLECULAR NEUROSCIENCE

Feng, Zhehui2 CA; Li, Dongdong; Fung, Peter C. W.; Pei, Zhong; Ramsden, David B.1; Ho, Shu-Leong

University Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong

1Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, UK

2Present Address: Department of Experimental Therapeutics, Box 019, UT M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA

CACorresponding Author: [email protected]

Received 19 May 2003; accepted 21 July 2003

Abstract

The primary lesion in Parkinson's disease is the death of dopaminergic neurons in the substantia nigra. The role of cyclooxygenase (COX)-2 in the etiology of Parkinson's disease was explored using COX-2 gene knockout mice. Mortality after injection of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP, a chemical known to cause parkinsonism in humans) in heterozygous COX-2-deficient mice was lower than that in wild-type mice. The number of tyrosine hydroxylase immunoreactive neurons in the substantia nigra pars compacta of MPTP-treated wild-type mice declined to a greater extent than in heterozygous mice. Inhibition of COX-2 protein expression decreased the lesion caused by MPTP and protected the dopaminergic neurons in substantia nigra pars compacta. This result suggested that inhibition of COX-2 has potential therapeutic implications.